Susan E Ozanne

Susan E Ozanne
University of Cambridge | Cam

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374
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Publications

Publications (374)
Article
Introduction: Metformin is the first-line pharmacological treatment for gestational diabetes in many countries. Although effective at improving maternal glycaemia, metformin readily crosses the placenta and could directly affect the fetus. Indeed, metformin exposure in utero increases postnatal adiposity. However, other long-term effects on offspr...
Article
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The agouti viable yellow (Avy) allele is an insertional mutation in the mouse genome caused by a variably methylated intracisternal A particle (VM-IAP) retrotransposon. Avy expressivity is sensitive to a range of early-life chemical exposures and nutritional interventions, suggesting that environmental perturbations can have long-lasting effects on...
Article
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Background: Metformin is commonly used to treat gestational diabetes mellitus. This study investigated the effect of maternal metformin intervention during obese glucose-intolerant pregnancy on the gonadal white adipose tissue (WAT) of 8-week-old male and female mouse offspring. Methods: C57BL/6J female mice were provided with a control (Con) or...
Article
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Introduction: Due to increasing lifespan, global aging rates are rising rapidly and age-associated diseases are increasing. To ensure that health span is concomitant with life span, a greater understanding of cellular mechanisms of aging is important. Methods: Telomere length analysis from a wide range of tissues from weaning, young adult, and m...
Article
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The genetic mechanisms that determine the size of the adult pancreas are poorly understood. Imprinted genes, which are expressed in a parent-of-origin-specific manner, are known to have important roles in development, growth and metabolism. However, our knowledge regarding their roles in the control of pancreatic growth and function remains limited...
Preprint
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Objective: We systematically assessed the impact of metformin treatment on maternal pregnancy outcomes. Data Sources: PubMed, Ovid Embase, Medline, Web of Science, ClinicalTrials.gov and Cochrane databases were systematically searched (inception-19th November 2020). Methods of Study Selection: Randomized controlled trials reporting pregnancy outcom...
Preprint
Full-text available
The genetic mechanisms that determine the size of the adult pancreas are poorly understood. Here we demonstrate that many imprinted genes are highly expressed in the pancreatic mesenchyme, and explore the role of Igf2 in-vivo. Mesenchyme-specific Igf2 deletion results in acinar and beta-cell hypoplasia, postnatal whole-body growth restriction and m...
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Telomeres are protein-bound regions of repetitive nucleotide sequences (TTAGGG) at the end of human chromosomes, and their length is a marker of cellular aging. Intrauterine growth restriction is associated with shorter blood cell telomeres at birth and individuals with type 2 diabetes have shorter telomeres. Individuals with a low birth weight (LB...
Data
Table S1: Primer sequences and product length for reported genes
Article
Variation in early-life conditions can trigger developmental switches that lead to predictable individual differences in adult behaviour and physiology. Despite evidence for such early-life effects being widespread both in humans and throughout the animal kingdom, the evolutionary causes and consequences of this developmental plasticity remain uncl...
Article
Animal models have been indispensable in elucidating the potential causative mechanisms underlying the effects of maternal diet on offspring health. Of these, the mouse has been widely used to model maternal overnutrition and/or maternal obesity and to study its effects across one or more generations. This review discusses recent findings from mous...
Preprint
Full-text available
Maternal obesity increases type 2 diabetes (T2D) risk in the offspring. Given that nearly half of women of child-bearing age in many populations are currently overweight/obese, it is key that we improve our understanding of the impact of the in utero/early life environment on offspring islet function. Using a well-established mouse model of diet-in...
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Chronic fetal hypoxia is a common complication observed in human pregnancy, impacting pregnancies across global contexts. Exposure to chronic intrauterine hypoxia has major short- and long-term consequences for offspring health. However, the impact of chronic gestational hypoxia on female reproductive system development is unknown. We aimed to unde...
Article
Maternal obesity in pregnancy is associated with neurobehavioral problems in the offspring. Establishing causality has been challenging in existing human studies, due to confounding by genetic and postnatal environment. Animal experiments can improve our understanding of this association. This systematic review examined the effects of maternal obes...
Article
Full-text available
Key points: Exposure to chronic hypoxia during gestation influences long-term health and development, including reproductive capacity, across generations. If the peri-conceptual environment, in the developing oviduct, is affected by gestational hypoxia, then this could have implications for later fertility and the health of future generations. In...
Article
Full-text available
Obesity before and during pregnancy leads to reduced offspring cardiometabolic health. Here, we systematically reviewed animal experimental evidence of maternal obesity before and during pregnancy and offspring anthropometry and cardiometabolic health. We systematically searched Embase and Medline from inception until January 2018. Eligible publica...
Chapter
It is an important part of many rodent studies to assess reproductive capacity in the female. Animal models that involve exposure to organic compounds, teratogenicity studies, or exposure to suboptimal environments during early development often result in deficits in female fertility. In addition to longitudinal physiology assays of fecundity, ther...
Chapter
The prevalence of age-associated disease is increasing at a striking rate globally and there is evidence to suggest that the ageing process may actually begin before birth. It has been well-established that the status of both the maternal and early postnatal environments into which an individual is exposed can have huge implications for the risk of...
Article
Full-text available
Research question: The physiological processes of pregnancy and lactation require profound changes in maternal metabolism and energy balance. The timescale of metabolic reversion after pregnancy, in particular post-partum weight loss, is highly variable between individuals. Currently, mechanisms influencing post-partum metabolic recovery are not w...
Article
Full-text available
Aims: Intra-uterine growth restriction (IUGR) followed by accelerated postnatal growth is associated with an increased risk of obesity and type 2 diabetes. We aimed to determine central and peripheral insulin sensitivity in mice that underwent IUGR followed by postnatal catch-up growth and investigate potential molecular mechanisms underpinning th...
Article
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Integrating functional and molecular levels, we investigated the effects of maternal treatment with a xanthine oxidase inhibitor on the programming of cardiac dysfunction in adult offspring using an established rat model of hypoxic pregnancy. Female Wistar rats were divided into normoxic or hypoxic (13% O2) pregnancy±maternal allopurinol treatment...
Article
The early life environment experienced by an individual in utero and during the neonatal period is a major factor in shaping later life disease risk-including susceptibility to develop obesity, diabetes, and cardiovascular disease. The incidence of metabolic disease is different between males and females. How the early life environment may underlie...
Article
Full-text available
Reduced fetal nutrition and rapid postnatal growth accelerates the aging phenotype in many organ systems; however, effects on the immune system are unclear. We addressed this by studying the thymus from a rat model of developmental programming. The recuperated group was generated by in utero protein restriction, followed by cross-fostering to contr...
Article
Full-text available
Objective Obesity during pregnancy is associated with an elevated risk of cardiovascular disease in the offspring. With increased numbers of women entering pregnancy overweight or obese, there is a requirement for targeted interventions to reduce disease risk in future generations. Using an established murine model of maternal obesity during pregna...
Article
Full-text available
'Developmental programming', which occurs as a consequence of suboptimal in utero and early environments, can be associated with metabolic dysfunction in later life, including an increased incidence of cardiovascular disease and type 2 diabetes, and predisposition of older men to sarcopenia. However, the molecular mechanisms underpinning these asso...
Article
Full-text available
Aims: Obesity during pregnancy increases risk of cardiovascular disease (CVD) in the offspring and individuals exposed to over-nutrition during fetal life are likely to be exposed to a calorie-rich environment postnatally. Here, we established the consequences of combined exposure to a maternal and post-weaning obesogenic diet on offspring cardiac...
Article
Full-text available
AIMS Obesity during pregnancy increases risk of cardiovascular disease (CVD) in the offspring and individuals exposed to over-nutrition during fetal life are likely to be exposed to a calorie-rich environment postnatally. Here, we established the consequences of combined exposure to a maternal and post-weaning obesogenic diet on offspring cardiac s...
Article
Full-text available
Background: The early life environment experienced by an individual in utero and during the neonatal period is a major factor in shaping later life disease risk-including susceptibility to develop obesity, diabetes, and cardiovascular disease. The incidence of metabolic disease is different between males and females. How the early life environment...
Article
Much telomere loss takes place during the period of most rapid growth when cell proliferation and potentially energy expenditure are high. Fast growth is linked to reduced longevity. Therefore, the effects of somatic cell proliferation on telomere loss and cell senescence might play a significant role in driving the growth-lifespan trade-off. While...
Article
Full-text available
Developmental programming phenotypes can be recapitulated in subsequent generations not directly exposed to the initial suboptimal intrauterine environment. A maternal low-protein diet during pregnancy and postnatal catch-up growth ('recuperated') alters insulin signaling and inflammation in rat offspring (F1-generation). We aimed to establish if t...
Article
Full-text available
Developmental programming phenotypes can be recapitulated in subsequent generations not directly exposed to the initial suboptimal intrauterine environment. A maternal low-protein diet during pregnancy and postnatal catch-up growth (‘recuperated’) alters insulin signaling and inflammation in rat offspring (F1-generation). We aimed to establish if t...
Article
Full-text available
Background: Mammalian species exhibit a wide range of lifespans. To date, a robust and dynamic molecular readout of these lifespan differences has not yet been identified. Recent studies have established the existence of ageing-associated differentially methylated positions (aDMPs) in human and mouse. These are CpG sites at which DNA methylation d...
Article
Mammalian species exhibit a wide range of lifespans. To date, a robust and dynamic molecular readout of these lifespan differences has not yet been identified. Recent studies have established the existence of ageing-associated differentially methylated positions (aDMPs) in human and mouse - CpG sites at which DNA methylation dynamics shows a signif...
Chapter
Identifying microRNA (miRNA) signatures in animal tissues is an essential first step in studies assessing post-transcriptional regulation of gene expression in health or disease. Small RNA sequencing (sRNA-Seq) is a next-generation sequencing-based technology that is currently considered the most powerful and versatile tool for miRNA profiling. Her...
Chapter
Accelerated cellular aging is known to play an important role in the etiology of phenotypes associated with developmental programming, such as cardiovascular disease and type 2 diabetes. Telomere length analysis is a powerful tool to quantify cellular aging. Here we describe a telomere length methodology, refined to quantify discrete telomere lengt...
Chapter
Poor nutrition during pregnancy leads to an increased risk of metabolic disorders and other diseases in the offspring. This can be modelled in animals through manipulation of the maternal diet. One such model is the maternal low-protein rat which gives rise to offspring characterized by insulin resistance. This chapter gives a detailed protocol for...
Article
Accelerated cellular aging is known to play an important role in the etiology of phenotypes associated with developmental programming, such as cardiovascular disease and type 2 diabetes. Telomere length analysis is a powerful tool to quantify cellular aging. Here we describe a telomere length methodology, refined to quantify discrete telomere lengt...
Article
Identifying microRNA (miRNA) signatures in animal tissues is an essential first step in studies assessing post-transcriptional regulation of gene expression in health or disease. Small RNA sequencing (sRNA-Seq) is a next-generation sequencing-based technology that is currently considered the most powerful and versatile tool for miRNA profiling. Her...
Article
Poor nutrition during pregnancy leads to an increased risk of metabolic disorders and other diseases in the offspring. This can be modelled in animals through manipulation of the maternal diet. One such model is the maternal low-protein rat which gives rise to offspring characterized by insulin resistance. This chapter gives a detailed protocol for...
Article
Much telomere loss takes place during the period of most rapid growth when cell proliferation and potentially energy expenditure are high. Fast growth is linked to reduced longevity. Therefore, the effects of somatic cell proliferation on telomere loss and cell senescence might play a significant role in driving the growth-lifespan trade-off. While...
Article
Full-text available
Ageing, a complex process that results in progressive decline in intrinsic physiological function leading to an increase in mortality rate, has been shown to be affected by early life nutrition. Accumulating data from animal and epidemiological studies indicate that exposure to a suboptimal nutritional environment during fetal life can have long-te...
Chapter
Type 2 diabetes mellitus is a multifactorial condition resulting in high fasting blood glucose levels. Although its diagnosis is straightforward, there is not one set of biomarkers or drug targets that can be used for classification or personalized treatment of individuals who suffer from this condition. Instead, the application of multiplex method...
Article
Developmental origins of health and disease (DOHaD) is the study of how the early life environment can impact the risk of chronic diseases from childhood to adulthood and the mechanisms involved. Epigenetic modifications such as DNA methylation, histone modifications and non-coding RNAs are involved in mediating how early life environment impacts l...
Article
Full-text available
Developmental origins of health and disease (DOHaD) is the study of how the early life environment can impact the risk of chronic diseases from childhood to adulthood and the mechanisms involved. Epigenetic modifications such as DNA methylation, histone modifications and non-coding RNAs are involved in mediating how early life environment impacts l...
Article
We systematically reviewed papers published in English between 1994 and October 2015 on how postnatal weight gain and growth affect neurodevelopment and metabolic outcomes in term-born small-for-gestational-age (SGA) infants. Two randomised trials reported that enriched infant formulas that promoted early growth also increased fat mass, lean mass a...
Article
Ageing, a complex process that results in progressive decline in intrinsic physiological function leading to an increase in mortality rate, has been shown to be affected by early life nutrition. Accumulating data from animal and epidemiological studies indicate that exposure to a suboptimal nutritional environment during fetal life can have long-te...
Article
Full-text available
We systematically reviewed papers published in English between 1994 and October 2015 on how postnatal weight gain and growth affect neurodevelopment and metabolic outcomes in term-born small-for-gestational-age (SGA) infants. Two randomised trials reported that enriched infant formulas that promoted early growth also increased fat mass, lean mass a...
Article
Full-text available
Key points In the Western world, obesogenic diets containing high fat and high sugar (HFHS) are commonly consumed during pregnancy, although their effects on the metabolism of the mother, in relation to feto‐placental glucose utilization and growth, are unknown. In the present study, the consumption of an obesogenic HFHS diet compromised maternal g...
Chapter
Stable isotope labelling by amino acids in cell culture (SILAC) is a technique that allows proteomic profiling of cells. In this chapter we describe a protocol for the identification and quantification of newly synthesised proteins. The methodology can be applied to any cultured cell system with relevance to schizophrenia, affective disorders and a...
Article
Epidemiological studies have shown that periods of poor nutrition during pregnancy can lead to an increased risk of metabolic and psychiatric disorders in the offspring. In addition, some individuals with disorders such as schizophrenia show signs of impaired insulin signalling. These findings indicate that there may be a link between metabolism an...
Article
Full-text available
Previous studies have shown that maternal diet-induced obesity leads to increased risk of type 2 diabetes in offspring. The current study investigated if weaning onto an obesogenic diet exaggerated the detrimental effects of maternal diet-induced obesity in adipose tissue. Maternal obesity and offspring obesity led to reduced expression of key insu...
Article
Previous studies have shown that maternal diet-induced obesity leads to increased risk of type 2 diabetes in offspring. The current study investigated if weaning onto an obesogenic diet exaggerated the detrimental effects of maternal diet-induced obesity in adipose tissue. Maternal obesity and offspring obesity led to reduced expression of key insu...
Article
Full-text available
The prevalence of obesity during pregnancy continues to increase at alarming rates. This is concerning as in addition to immediate impacts on maternal wellbeing, obesity during pregnancy has detrimental effects on the long-term health of the offspring through non-genetic mechanisms. A major knowledge gap limiting our capacity to develop interventio...
Article
Full-text available
The prevalence of obesity during pregnancy continues to increase at alarming rates. This is concerning as in addition to immediate impacts on maternal wellbeing, obesity during pregnancy has detrimental effects on the long-term health of the offspring through non-genetic mechanisms. A major knowledge gap limiting our capacity to develop interventio...
Chapter
Stable isotope labelling by amino acids in cell culture (SILAC) is a technique that allows proteomic profiling of cells. In this chapter we describe a protocol for the identification and quantification of newly synthesised proteins. The methodology can be applied to any cultured cell system with relevance to schizophrenia, affective disorders and a...
Chapter
Epidemiological studies have shown that periods of poor nutrition during pregnancy can lead to an increased risk of metabolic and psychiatric disorders in the offspring. In addition, some individuals with disorders such as schizophrenia show signs of impaired insulin signalling. These findings indicate that there may be a link between metabolism an...